A rising tide with liraglutide

# # # #

A class of diabetes drugs called GLP-1 receptor agonists have exhibited neuroprotective properties in models of Parkinson’s, and a Phase IIb clinical trial produced encouraging.

This research has led to a number of parties to start investigating new and old GLP-1 receptor agonists for their potential to slow the progression of Parkinson’s.

Recently, the results of a second Phase II clinical trial investigating a GLP-1 agonist were announced. The agonist being tested was liraglutide. 

In today’s post, we will discuss what GLP-1 receptor agonists are, what research has been conducted in PD, and look at the recent clinical trial announcement.

# # # #


static1.squarespace

The name “Golden Goose Award” doesn’t really conjure images of an inspirational kind of accomplishment. It does not suggest the same kind of gravitas that the Nobel prize carries. 

In fact, it sounds rather comical: The golden goose award? Sounds like a children’s book writers award.

 And yet…

The Award was originally established in 2012 with the goal of celebrating researchers whose seemingly odd or obscure federally funded research turned out to have a significant and positive impact on society as a whole.

And despite the name, it is a very serious award – past Nobel prize winners (such as Roger TsienDavid H. Hubeland Torsten N. Wiesel) are among the awardees.

In 2013, it was awarded to Dr John Eng, an endocrinologist from the Bronx VA Hospital.

rudw9esurtnukjwruf7q

Dr John Eng. Source: Health.USnews

What did Dr Eng do to deserve the award?

Continue reading “A rising tide with liraglutide”

GCase: Mutants matter?

# # # #

Tiny genetic variations in a region of DNA called the GBA gene are associated with an increased risk of developing Parkinson’s. The information in the GBA gene provides the instructions for making an enzyme (called GCase) which is involved with waste disposal inside of cells.

Individuals with Parkinson’s who carry a variation in their GBA gene typically have low levels of GCase activity, so researchers have been attempting to identify therapeutic molecules that will enhance the level and activity of GCase as an approach towards slowing the progression of Parkinson’s.

Recently, however, new research has provide novel insights into how the biology of GCase pathway may be affected in individuals with Parkinson’s who carry a GBA genetic variation. 

In today’s post, we will explain what the GBA gene and GCase enzyme are, review the new research, and consider the potential implications of these findings.

# # # #


Prof Sulzer. Source: Youtube

Professor David Sulzer is one individual in the scientific research community who truly fascinates me.

In addition to being at the absolute top of his game academically (he is a professor of Psychiatry, Neurology, Pharmacology at Columbia University and maintains a very large research group investigating neurodegenerative conditions), he is also a composer and musician with a discography that any professional artists would be extremely proud of (his recording alias is Dave Soldier).

He’s also written books (for example Music Math and Mind“).

Source: Twitter

Where he finds the time to do all of these thing I do not know, but I really like the combination of art and science.

Oh, and did I forget to mention the Thai Elephant Orchestra?

I’m sorry: The what?!?

Just watch:

They have released three CDs and the band grew up to 14 elephants.

Fascinating, but what does this have to do with Parkinson’s?

Continue reading “GCase: Mutants matter?”

The road ahead: 2022

# # # #

The first post at the start of each year on the SoPD website tries to provide an overview of where things are in the search for ‘disease modifying’ therapies for Parkinson’s. 

It is an exercise in managing expectations as well as discussing what research events are scheduled for the next year so that we can keep an eye out for them. I will also note aspects of ongoing research where I will be hoping to see an update on progress. Obviously, where 2022 will actually end is unpredictable, but an outline of what is coming over the next 12 months will hopefully provide the community with a useful resource.

While there is a great deal of interesting research exploring the causes of the condition, the genetics and biology of the condition, novel symptomatic therapies, and other aspects of Parkinson’s, the primary focus in this post is on the clinical trial research seeking to slow, stop or reverse the condition.

In this post, we will hopefully give readers a taste of what the landscape looks like for clinical research focused on disease modification for Parkinson’s.

# # # #


David Livingstone. Source: CT

If you have men who will only come if they know there is a good road, I don’t want them. I want men who will come if there is no road at all.

David Livingstone

The Scottish physician Dr David Livingstone – missionary and explorer – led an interesting life.

Most of us only know of him for his fabled adventures in Africa. But they are made more remarkable given his extremely humble beginnings.

Born into poverty, Livingstone started his working life at 10 years of age in a cotton factory, where he worked from 6am till 8pm everyday. He somehow managed to get some schooling around those work shifts, and his impoverished family saved enough money so that he could attend Anderson’s University (Glasgow) when he was 23.

Cotton factory (Source)

How he got from the cotton factory to becoming the first European to cross the width of southern Africa (as well as ‘discovering’ the Mosi-oa-Tunya waterfalls – aka Victoria Falls), was one of the great rag-to-riches stories of Victorian times and making him something of a celebrity of the age.

Mosi-oa-Tunya waterfalls. Source: Cblacp

But his mapping out of central Africa was his greatest legacy.

As a biographer wrote “Through him, the centre of Africa ceased to be a dark, unknown space on the map and became a real place, full of interesting human beings [and] wonderful wildlife. . . .” (Source)

It has to be acknowledged, however, that Livingstone was not able to explore the entirety of the Zambezi River system himself so he would often ask the local people for information, and he would then incorporate their contributions into his maps.

Livingstone’s travels (Source)

“We travel in the company of men who are well acquainted with parts of the country by personal observation… They soon see that we are interested in the courses of rivers, names of hills, tribes…and make enquiries among the villagers to whom we come. Drawings are made on the ground and parts pointed out that bearings may be taken and comparisons drawn from the views of different individuals. We thus gain a general idea of the whole country” (Source)

It makes one appreciate that maps are collaborative efforts, incorporating the efforts of lots of different parties. And it is only by going through the process of mapping something out that we start to understand it, know our place in it, observe the limitations to our knowledge, and perhaps find something of what we are looking for.

At the start of each year, the SoPD publishes a horizon scanning post where we take a Livingstone-like approach towards mapping out the landscape of clinical research focused on disease modification for Parkinson’s, and what follows is the 2022 version.

Continue reading “The road ahead: 2022”

ADepTing to the UCB-Novartis deal

# # # #

Alpha synuclein has long been viewed at “Public enemy #1” by the Parkinson’s research community. This sticky, abundant protein starts to cluster (or aggregate) in Parkinson’s.

There have been several attempts to reduce levels of the protein floating around outside of cells (using “immunotherapy” approaches)

But now clinical research is ramping up to determine if reducing aggregated alpha synuclein levels in the brain could help to slow/stop the progression of the condition.

In today’s post, we will look at three different lines of clinical research focused on small molecule inhibitors of alpha synuclein aggregation. 

# # # #


When someone mentions the pharmaceutical firm Novartis, it feels like the company has been around forever, but it is actually not that old.

It was created in March 1996 via the merger of two Swiss companies: Ciba-Geigy and Sandoz. The roots of those companies can be traced back more than 250 years, but the combined entity is still a spring chicken compared to many of its major competitors.

The name Novartis results from the combination of two words “Nova Artes”, which means new art and innovation in simple forms, but there is little in what the company does that is ‘simple’. A good example of this was their block buster cancer drug Gleevec/Glivec (imatinib) which was developed by careful “rational drug design” for very specific types of cancer.

Source: NCBI

The reputation for Swiss precision seems to flow through this company and they are always making very carefully placed bets.

Which makes their news this week rather interesting.

What news did they have?

Continue reading “ADepTing to the UCB-Novartis deal”

Mo better for TEVA with Modag?

 

# # # #

This week the pharmaceutical company TEVA Pharmaceuticals Industries Ltd has announced a deal with a small German biotech firm called MODAG.

The two companies are forming a strategic collaboration on the exclusive worldwide licensing and development of MODAG’s lead compound anle138b.

Anle138b is a small molecule inhibitor of the believed to be toxic forms of the Parkinson’s-associated protein alpha synuclein.

In today’s post, we will discuss what is known about anle138b and the implications of this new partnership.

# # # #


Source: SLE

In 1901, Haim Salomon and his brother-in-law Moshe Levin established a small wholesale drug business, near the Nablus Gate in Jerusalem. They called it “Salomon and Levin”. A few years later, Yitzhak Elstein, another of Haim Salomon’s brothers-in-law, joined the firm and they changed the name of the company to SLE – Salomon Levin and Elstein.

Source: SLE

From these humble beginning, grew a pharmaceutical juggernaut that we know today as TEVA Pharmaceuticals.

TEVA – meaning “Nature” in Hebrew – is now an international producer of pharmaceutical agents, with 40,000 employees working across 65 manufacturing facilities in more than 30 countries. The company has a portfolio of more than 3,500 medicines, and they produce approximately 85 billion tablets and capsules per year (Source).

Does TEVA produce any drugs for Parkinson’s?

Yes, Azilect (rasagiline) – an approved monoamine-oxidase B inhibitor for the treatment of Parkinson’s – was developed by Teva Pharmaceuticals.

In addition, they are actively developing novel therapies. And this week they signed a really interesting deal to collaborate with a small German biotech company called MODAG.

What does MODAG do?

Continue reading “Mo better for TEVA with Modag?”

Repurposing bumetanide for Alzheimer’s

# # # #

Bumetanide (Bumex) is a diuretic drug (a medication that removes water, by increasing the production of urine). It is used to treat swelling caused by heart failure or liver or kidney disease. It is a widely used drug that has been well characterised in clinical use.

Recently researchers conducted a screening study to identify clinically available agents that might be useful in the treatment of the cognitive decline associated with a genetic risk factor for Alzheimer’s: APOE4 

The top drug identified in their study was bumetanide.

In today’s post we will discuss what APOE4 is, we will review the results of the new study, and we will look at why these findings could be interesting for Parkinson’s.

# # # #


Source: Pharmacysafety

Many years ago, I was at a patient-research interaction event and a world-leading genetics researcher was asked by someone in the audience if they had had their DNA sequenced.

They said ‘no‘.

The person asking the question frowned and asked ‘why not? You have all the technology and knowledge – don’t you want to know more about yourself?

The researcher replied “No. Having your DNA sequenced should not be taken lightly. You might learn stuff about yourself that you don’t want to know

They used the example of possibly being an APOE4 carrier (who have a higher risk of cognitive decline during aging). The geneticist declared that they would rather not know that kind of information for fear of the impact that it could have on their life.

The questioner respected the honest answer and the conversation that followed was really interesting. More recently, however, as we have learned more about APOE4 and new drugs are being targeted at this risk factor, I have often wondered if their decision would still stand. Are we approaching an age when we might want to know if we are APOE4 carriers?

Hang on a moment. What is this APOE4 thing?

Continue reading “Repurposing bumetanide for Alzheimer’s”

Making a (G)case for quetiapine

# # # #

Drug repurposing (repositioning, reprofiling or re-tasking) is a strategy of identifying novel uses for clinically approved (or experimental) drugs that fall outside the scope of the original medical indication.

Many drug repurposing efforts have started with screening experiments, looking for drugs with certain properties.

Recently, researchers conducted a drug repurposing screening experiment for molecules that enhance a Parkinson’s protein (called GCase) and they found an interesting result: the antipsychotic medication quetiapine.

In today’s post, we will explain what GCase does, review what the new study found, and consider what could happen next.

# # # #


At the recent “Rallying to the Challenge” meeting (which was conducting in parallel with the Van Andel Institute‘s “Grand Challenges in Parkinson’s Disease“), I was asked by Cure Parkinson’s to present on why the biology surrounding genetic risk factors – like variation in the GBA and LRRK2 genes – are important targets for potential therapeutic intervention in Parkinson’s (my presentation starts at 2 hours & 10 minutes into the video above).

Specifically, I was asked to discuss why they are important targets not just for individuals carrying the genetic variations in these genes, but for the wider Parkinson’s community in general. And it is a good question.

How could inhibitors of LRRK2 or enhancers of GCase activity possibly be useful to individuals with idiopathic (spontaneous or not associated with a genetic risk factor) Parkinson’s?

My answer was rather simple.

What was it?

Continue reading “Making a (G)case for quetiapine”

Farnesol: The farnesylator of PARIS

# # # #

A build up of “PARkin Interacting Substrate” (or PARIS) protein has been proposed as one potential mediator of the pathology observed in some cases of Parkinson’s. The accumulation of this protein leads to the inhibition of a key protein called PGC-1α, which is a neuroprotective protein that helps to keep cells alive.

For sometime, researchers have been searching for molecules that can act as inhibitors of PARIS, in the hope that blocking PARIS would allow PGC-1α to act freely. Such an agent could have potential as novel treatment for Parkinson’s.

This week a research report was published that describes one possible PARIS inhibitor. It is called farnesol.

In today’s post, we will look at the biology behind PARIS, review the new report, and discuss what exactly is known about farnesol.

# # # #


Pont Royal et Musée d’Orsay. Source: Wikipedia

Paris has a special place in my heart for several reasons.

The main one: I proposed to my wife there on the Pont Royal.

We had planned a day out in London, but once we got down to Waterloo “for lunch at a special restaurant“, I surprised her with two Euro Star tickets and we were off on the train for Paris – just like that (I might look the hardened tough guy on the outside, but deep down I am really just a tragic romantic).

And that night, after “dinner at a special restaurant” shortly before 10pm as we were crossing the middle of the Pont Royal, and a small miracle occurred: the traffic lights stopped traffic in both directions.

Source: Pixels

Seizing our chance moment alone, I dropped to one knee and asked (read: begged).

Now, if she had said ‘no thanks‘, I had a back up plan: Jump over the side of the bridge, float down the Seine some ways, climb out and then join the Foreign Legions the next day as a mute (je suis muet”).

But she didn’t say no (let’s call that the second small miracle) and thankfully for my fragile ego’s sake there wasn’t a lengthy deliberation.

When the traffic lights changed and traffic started to flow again, we received some enthusiastic honks of the klaxons (horns) as I got up and we headed off to alert our parents. It was a really nice moment.

I was recalling this moment, this week when a different type of Paris was being discussed in the news.

What do you mean “a different type of Paris”?

Continue reading “Farnesol: The farnesylator of PARIS”

The Bluerockers have started

# # # #

On the 8th June, BlueRock Therapeutics put out a press release announcing that the first participant in their Phase I clinical trial of cell transplantation for Parkinson’s had been dosed (Click here to read the press release).

The initiation of this clinical trial by the company is a major step forward for them and for the wider field of regenerative therapies.

In today’s post, we will look at what cell transplantation is, recent developments in clinical trials, and what the immediate future holds. 

# # # #


Source: The Scientist

Here on the SoPD, we work around the idea that any “curative therapy” for Parkinson’s is going to require three core components:

  1. A disease halting mechanism
  2. A neuroprotective agent
  3. Some form of restorative therapy

Parkinson’s is a progressive neurodegenerative condition, meaning that symptoms are gradually going to get worse over time. Thus, the first and most critical component of any ‘cure’ for Parkinson’s involves a treatment that will slow down or halt the progression of the condition.

Once such a therapy has been identified, it will be necessary to rejuvenate and protect the remaining cells. So, some form of neuroprotective therapy that can help bring sick or dying cells back to life will be required.

Such a treatment will also provide a nurturing environment for the third part of the ‘cure’: A restorative treatment. New cells will be required to replace the lost function.

Now, the bad news is (as far as I am aware) there is no single treatment currently available (or being tested) that can do all three of these things. By this I mean that there is no “disease halting mechanism” therapy that can also replace lost brain cells. Nor is there a restorative therapy that stop the progression of the condition.

That statement can obviously be read as terrible news, but it shouldn’t.

Let me explain:

Continue reading “The Bluerockers have started”

The Anavex results

# # # #

This week some encouraging clinical trial results were announced by a biotech firm called Anavex Life Sciences.

The company had been testing their lead experimental therapy – a Sigma-1 receptor agonist called ANAVEX2-73 (also known as blarcamesine) – in 132 people with Parkinson’s disease dementia over a 14 week period.

The results are rather encouraging: significantly positive outcomes in both cognitive and motor symptoms.

In today’s post, we will explain what exactly “Sigma-1 receptor agonist” means, discuss what Parkinson’s disease dementia is, and review what we currently know about the results of the trial.

# # # #


Source: Pumpingmarvellous

A lot of clinical trials for disease modification in Parkinson’s are focused on targeting well known proteins that are believed to be associated with underlying biology of the condition, such as alpha synuclein, LRRK2, and GBA. We discuss these on a regular basis here on the SoPD.

There are, however, a large number of trials investigating less well known targets.

And this week we received news that one of these clinical trials had some positive results.

Source: Thestreet

The study was conducted by the biotech company Anavex Life Sciences and it involved their lead experimental therapy ANAVEX2-73 (also known as blarcamesine).

ANAVEX2-73 is a Sigma-1 receptor agonist.

What does that mean?

Continue reading “The Anavex results”